Associations among within-litter differences in early mothering received and later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats

Abstract

This article is part of a Special Issue "Parental Care". The effects of differential maternal care received on offspring phenotype in rodents has been extensively studied between litters, but the consequences of differential mothering within litters on offspring neurobehavioral development have been rarely examined. We here investigated how variability in maternal care received among female rat siblings (measured four times daily on postnatal days 4, 6, 8, and 10) relates to the siblings' later emotional and maternal behaviors. As previously reported, we found that some female pups received up to three times more maternal licking bouts compared to their sisters; this difference was positively correlated with the pups' body weights. The number of maternal licking bouts that females received was negatively correlated with their later neophobic behaviors in an open field during periadolescence, but positively correlated with their anxiety-related behavior in an elevated plus maze during adulthood. Licking received was also positively correlated with females' later likelihood to retrieve pups in a maternal sensitization paradigm. In addition, females' neophobia during adolescence and anxiety-related behavior during adulthood predicted some aspects of both postpartum and sensitized maternal responsiveness. Medial prefrontal cortex expression of tryptophan hydroxylase-2 (TPH2; enzyme necessary for serotonin synthesis) was negatively associated with early maternal licking received. Interestingly, cortical TPH2 was positively associated with the maternal responsiveness of sensitized virgins but negatively associated with it in postpartum females. These results indicate that within-litter differences in maternal care received is an often neglected, but important, contributor to individual differences in offspring socioemotional behaviors as well as to the cortical serotonin neurochemistry that may influence these behaviors.

Inter‐individual maternal care received and genotype interactions affect dopaminergic phenotypes in female rat offspring

“…Other studies, including our own, have demonstrated that mothers also show variation in their maternal licking to different pups within the litter . We found that total inter‐individual LG received is associated with differences in stress reactivity at adulthood .…”

“…[16][17][18] Other studies, including our own, have demonstrated that mothers also show variation in their maternal licking to different pups within the litter. [19][20][21][22][23][24] We found that total inter-individual LG received is associated with differences in stress reactivity at adulthood. 23,24 The effects of average licking bout length received by individual pups on their later-life behaviour have not been explored.…”

Extensive juvenile “babysitting” facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase‐2 expression in female laboratory rats

“…Work by Olazábal et al (2004) also supports this idea, in that they found that juveniles have higher tissue content of serotonin and its metabolite compared to nulliparous adult female rats in brain regions involved in maternal behavior including the medial preoptic area (mPOA). We have shown that postpartum rats have higher serotonin turnover in the mPOA and nearby bed nucleus of the stria terminalis compared to nulliparous adult females (Lonstein et al, ; Smith et al, ), and that cortical TPH2 is positively associated with maternal responsiveness in sensitized virgins (Ragan et al, ). Thus, aspects of the midbrain and forebrain serotonin systems are upregulated in female rats that are prone to display mothering (i.e., juveniles, nulliparous adults with juvenile alloparental experience, and postpartum dams) compared to maternally resistant females (i.e., nulliparous inexperienced adults).…”

“…Another factor that may have been relevant for our alloparentally experienced females in Experiment 2 is that rodent mothers that are simultaneously pregnant and lactating are less responsive to offspring cues, spend more time outside the nest, and nurse less often (Konig & Markl, 1987;Krackow & Hoeck, 1989;Naguib, Kober, & Trillmich, 2010;Uriarte et al, 2008). Daughters that receive less maternal care are less prone to being maternally sensitized as adults (Champagne, Diorio, Sharma, & Meaney, 2001;Ragan, Harding, & Lonstein, 2015), and this may have countered any positive influence of alloparental experience on our females' later maternal responsiveness.…”

The Drosophila foraging gene human orthologue PRKG1 predicts individual differences in the effects of early adversity on maternal sensitivity

“…The functional aspects of this interaction could be addressed by measuring gene expression/activity differences arising from different combinations of PRKG1 and serotonin transporter genetic variants in cell culture. Recent rat studies show a role for serotonin system in regulation of maternal behavior and in the effect of maternal licking on serotonin-based pup development (Yang et al, 2015; Ragan, Harding, & Lonstein, 2016). Hence, regulation of the serotonin transporter by PRKG1 and its interaction with early adversity provides one potential biological mechanism for the effects observed in the present study.…”